OVERALL CONNECT-TBI Program Summary In the past several decades, there has been steadily increasing attention to the neuropathological effects of traumatic brain injury (TBI). Intense media attention has focused on the association of repetitive mild TBI with contact sports and have highlighted the risk of neurodegenerative changes including the widely discussed chronic traumatic encephalopathy (CTE). Unfortunately, little is known about the broader process of TBI- Related Neurodegeneration (TRenD) which encompasses a complex spectrum of pathologies induced by TBI, across all mechanisms and severity levels of injury. Arguably the greatest inhibitor of progress in this field is the limited number of suitable human brain tissue samples and their distribution among disparate research and clinical institutions. To overcome this, the proposed center without walls known as COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI) will be comprised of 26 leading expert investigators in TBI from 12 renowned institutions to generate an unparalleled, comprehensive neuropathological and clinical data resource and conduct a comprehensive research effort into the spectrum of pathologies in all types and severities of TBI. Three Cores ? Administrative, Brain Bank, and Data Coordinating ? will coordinate and support the collation and examination of over 2800 existing TBI case materials and over 7000 samples from patients with related neurodegenerative disorders. Furthermore, CONNECT-TBI will establish tissue donation protocols for ongoing sample enrollment in the coming years. This resource will be utilized to generate a consensus in the operational criteria for the diagnosis of TReNDs across all range and subtypes and to evaluate the extent and distribution of all neuropathologies resulting from TBI exposure. Furthermore, the center will seek to contrast the phenotypes of TReNDs with that of wider neurodegenerative disease and with aging processes. In all, the CONNECT-TBI collaboration will represent a broad, comprehensive exploration of the intricate neuropathological changes following TBI.